Eukaryotic cytoplasmic messenger RNAs (mRNAs) are either translated in association with polysomes or are present as non-translated messenger ribonucleoprotein (mRNP) particles. The concentrations of individual mRNAs, which vary with mRNA half life, largely determine the nature of protein synthesis in the cell. Elucidation of the mechanisms which determine both mRNA turnover and translatability are therefore important in understanding the regulation of eukaryotic protein synthesis. The metabolic signals which determine the fate of cytoplasmic mRNAs are at present unclear, although there is some evidence that both mRNA turnover and translatability may be related to poly(A) metabolism. We have developed techniques to separate mRNAs on the basis of their 3' poly(A) length and to compare the mRNA content of these fractions by two dimensional gel analysis of their in vitro synthesized peptides. Individual mRNAs have very different steady state poly(a) size class distributions, thus suggesting they may indeed have differential rates of both poly(A) processing and degradation. We propose to investigate possible interrelationships between mRNA turnover, poly(A) metabolism and translatability and whether alterations in these parameters modulate the synthesis of specific proteins under different physiological conditions. We shall first determine possible precursor-product relationships between the polyadenylated and non-adenylated mRNA populations using pulse-labeling and hybridization techniques. The stabilities and translational efficiencies of a) different mRNAs with the same average poly(A) length and b) individual mRNAs cells in tissue culture will be used to determine the importance of specific alterations in mRNA turnover, poly(A) processing or translatability during their differentiation. These parameters will also be compared in rapidly growing and non-dividing neuroblastoma cells.